Nearly all models were fitted with the new-generation 7G-Tronic autobox, though this did receive further tweaks in 2010 to counter criticism of its sometimes lethargic pick-up from rest. Four-wheel drive was available in some overseas markets, but was not offered on right-hand drive vehicles.

With the introduction of the S 350 Bluetec, Mercedes rolled out a number of innovative new options, including Active Lane Keeping Assist, Active Blind Spot Assist, Attention Assist and Distronic Plus radar cruise control.